Weakening and wasting of the skeletal musculature is one of the cardinal signs of aging. Yet the causes of muscle degeneration during aging are unknown. In order to function properly, as well as to maintain a state of metabolic health, skeletal muscles require to be mechanically linked to the collagen of the connective tissues. This linkage occur at the ends of muscle fiber in a specialized region: the muscle tendon junction. Despite its isgnificance, this region has been very little studied. Our long term objectives include a) a molecular description of the mammalian muscle-tendon junction in normal adult muscles; b) an assessment of the alterations in this region that occur during the process of aging; and c) an assessment of the involvement of this region that occur during the process of aging; and c) an assessment of the involvment of this region in diseases of the skeletal musculature. In order to realize these aims we are studying by cytochemical, immunofluorescent and immuno-electron-microscopic techniques the presence and localization of acetylcholinesterase, alpha actinin, vinculin, filamin, type IV collagen, type V collagen, laminin, heparan sulfate proteoglycan and fibronectin in the muscle tendon junction of adult and aging mice. In addition, we are studying the localization of these macromolecules as well as the ultrastructural characteristics of muscle tendon junction which have been extracted in Triton X-100 under conditions which maintain the functional integrity of the muscle-tendon junction while removing all the cellular membranes. Any age-related alterations in the concentration, distribution, or detergent-resistance of these molecules will suggest molecular mechanisms which might underlie the process of aging in skeletal muscles. An understanding of this process could ultimately lead to the design of therapies to ameliorate the muscular weakening that accompanies musculoskeletal aging.